Bottom Line:
In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology.We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels.These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

ABSTRACTAnaphylaxis is a severe systemic allergic reaction which is rapid in onset and potentially fatal, caused by excessive release of mediators including histamine and cytokines/chemokines from mast cells and basophils upon allergen/IgE stimulation. Increased prevalence of anaphylaxis in industrialized countries requires urgent needs for better understanding of anaphylaxis. However, the pathophysiology of the disease is not fully understood. Here we report that the circadian clock may be an important regulator of anaphylaxis. In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology. We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels. These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

fig1: Histological and general locomotor analysis after induction of the bilateral electrolytic lesions of the SCN in mice. (a) The SCN of the mice was destroyed by bilateral electrolytic lesions and complete SCN destruction was ascertained by a postmortem histological analysis. Representative pictures of the staining in sham-operated mice (Sham) and mice with disrupted SCN (SCND) are shown. The arrow indicates the SCN area. (b) General locomotor activity of mice housed under LD 12 : 12 conditions was recorded and representative double-blot actograms of the drinking behavior of the mice during 30 days are shown. The black dots indicate the mouse locomotor activity. Horizontal open and solid bars indicate day and night, respectively. Please note that the drinking behavior (usually accompanied by food intake) became arrhythmic in mice with disrupted SCN (SCND).

Mentions:
In order to clarify the precise role of the circadian clock system in the generation of daily rhythms in systemic anaphylactic reaction, we examined the effects of SCN ablation on a time of day-dependent variations in passive systemic anaphylactic (PSA) reaction in mice, which is a representative model of anaphylaxis. We confirmed complete disruption of the SCN in mice by a histological check of lesion sites by Nissl staining after finishing all the experiments (Figure 1(a)) and by examining behavioral patterns (general locomotor activity with arrhythmicity) (Figure 1(b)).

fig1: Histological and general locomotor analysis after induction of the bilateral electrolytic lesions of the SCN in mice. (a) The SCN of the mice was destroyed by bilateral electrolytic lesions and complete SCN destruction was ascertained by a postmortem histological analysis. Representative pictures of the staining in sham-operated mice (Sham) and mice with disrupted SCN (SCND) are shown. The arrow indicates the SCN area. (b) General locomotor activity of mice housed under LD 12 : 12 conditions was recorded and representative double-blot actograms of the drinking behavior of the mice during 30 days are shown. The black dots indicate the mouse locomotor activity. Horizontal open and solid bars indicate day and night, respectively. Please note that the drinking behavior (usually accompanied by food intake) became arrhythmic in mice with disrupted SCN (SCND).

Mentions:
In order to clarify the precise role of the circadian clock system in the generation of daily rhythms in systemic anaphylactic reaction, we examined the effects of SCN ablation on a time of day-dependent variations in passive systemic anaphylactic (PSA) reaction in mice, which is a representative model of anaphylaxis. We confirmed complete disruption of the SCN in mice by a histological check of lesion sites by Nissl staining after finishing all the experiments (Figure 1(a)) and by examining behavioral patterns (general locomotor activity with arrhythmicity) (Figure 1(b)).

Bottom Line:
In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology.We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels.These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

ABSTRACTAnaphylaxis is a severe systemic allergic reaction which is rapid in onset and potentially fatal, caused by excessive release of mediators including histamine and cytokines/chemokines from mast cells and basophils upon allergen/IgE stimulation. Increased prevalence of anaphylaxis in industrialized countries requires urgent needs for better understanding of anaphylaxis. However, the pathophysiology of the disease is not fully understood. Here we report that the circadian clock may be an important regulator of anaphylaxis. In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology. We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels. These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.